Yun Li, PhD (Professor, Genetics and Biostatistics) was awarded an R56 grant from the National Institute of Aging (NIA) for her project titled “Study of selective cell and system vulnerability in Alzheimer’s disease”.
The project is focused on advancing the mechanistic understanding of AD, by first acquiring and harmonizing various in-house, protected and public data, encompassing bulk and single cell RNA-seq data, GWAS summary statistics, array genotyping and whole genome sequencing data, as well as myriads of functional genomic data. The team will analyze them using a suite of computational methods and bioinformatics tools to generate cell-type-specific mechanistic hypotheses. These hypotheses will be experimentally validated. The validations will be carried out in iPSC-derived neural cells (particularly excitatory neurons and microglia), as well as in iPSC-derived brain organoids involving diverse cell types including neurons, astrocytes, and microglia. In these iPSC-derived cells and organoids models, CRISPRi as well as knock-in experiments will be performed, to perturb the most promising putatively causal regulatory DNA elements, and evaluate the impact by measuring a cascade of molecular and cellular phenotypes including gene expression and AD related physiological phenotypes.